title: Commensal microbiota contributes to chronic endocarditis in TAX1BP1 deficient mice.
abstract: Tax1-binding protein 1 (Tax1bp1) negatively regulates NF-κB by editing the ubiquitylation of target molecules by its catalytic partner A20. Genetically engineered TAX1BP1-deficient (KO) mice develop age-dependent inflammatory constitutions in multiple organs manifested as valvulitis or dermatitis and succumb to premature death. Laser capture dissection and gene expression microarray analysis on the mitral valves of TAX1BP1-KO mice (8 and 16 week old) revealed 588 gene transcription alterations from the wild type. SAA3 (serum amyloid A3), CHI3L1, HP, IL1B and SPP1/OPN were induced 1,180-, 361-, 187-, 122- and 101-fold respectively. WIF1 (Wnt inhibitory factor 1) exhibited 11-fold reduction. Intense Saa3 staining and significant I-κBα reduction were reconfirmed and massive infiltration of inflammatory lymphocytes and edema formation were seen in the area. Antibiotics-induced 'germ free' status or the additional MyD88 deficiency significantly ameliorated TAX1BP1-KO mice's inflammatory lesions. These pathological conditions, as we named 'pseudo-infective endocarditis' were boosted by the commensal microbiota who are usually harmless by their nature. This experimental outcome raises a novel mechanistic linkage between endothelial inflammation caused by the ubiquitin remodeling immune regulators and fatal cardiac dysfunction.
authors.affiliation: Department of Microbiology, Faculty of Medicine, Oita University, Yufu, Oita, Japan ; Department of Ophthalmology, Faculty of Medicine, Oita University, Yufu, Oita, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Nakano
authors.forename: Emi
authors.initials: E
authors.lastname: Ikebe
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Tsukamoto
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Takahiro
authors.initials: T
authors.lastname: Mitsui
authors.forename: Takaaki
authors.initials: T
authors.lastname: Yahiro
authors.forename: Kunimitsu
authors.initials: K
authors.lastname: Inoue
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kawazato
authors.forename: Aiko
authors.initials: A
authors.lastname: Yasuda
authors.forename: Kanako
authors.initials: K
authors.lastname: Ito
authors.forename: Shigeo
authors.initials: S
authors.lastname: Yokoyama
authors.forename: Naohiko
authors.initials: N
authors.lastname: Takahashi
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Hori
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Shimada
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Moriyama
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Kubota
authors.forename: Katsushige
authors.initials: K
authors.lastname: Ono
authors.forename: Wataru
authors.initials: W
authors.lastname: Fujibuchi
authors.forename: Kuan-Teh
authors.initials: KT
authors.lastname: Jeang
authors.forename: Hidekatsu
authors.initials: H
authors.lastname: Iha
authors.forename: Akira
authors.initials: A
authors.lastname: Nishizono
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001483:Base Sequence; D002908:Chronic Disease; D017931:DNA Primers; D004696:Endocarditis / Q000188:drug therapy / Q000235:genetics / Q000382:microbiology*; D004797:Enzyme-Linked Immunosorbent Assay; D020869:Gene Expression Profiling; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D064307:Microbiota; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000900:Anti-Bacterial Agents; D017931:DNA Primers; D047908:Intracellular Signaling Peptides and Proteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D009363:Neoplasm Proteins; C523855:TAX1BP1 protein, mouse